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"Same day" ex-vivo regional gene therapy: a novel strategy to enhance bone repair

Virk, Mandeep S; Sugiyama, Osamu; Park, Sang H; Gambhir, Sanjiv S; Adams, Douglas J; Drissi, Hicham; Lieberman, Jay R
Ex-vivo regional gene therapy with bone marrow cells (BMCs) overexpressing bone morphogenetic protein-2 (BMP-2) has demonstrated efficacy in healing critical sized bone defects in preclinical studies. The purpose of this preclinical study was to compare the osteoinductive potential of a novel "same day" ex-vivo regional gene therapy versus a traditional two-step approach, which involves culture expansion of the donor cells before implantation. In the "same day" strategy buffy coat cells were harvested from the rat bone marrow, transduced with a lentiviral vector-expressing BMP-2 for 1 hour and implanted into a rat femoral defect in the same sitting. There was no significant difference (P = 0.22) with respect to the radiographic healing rates between the femoral defects treated with the "same day" strategy (13/13; 100%) versus the traditional two-step approach (11/14; 78%). However, the femoral defects treated with the "same day" strategy induced earlier radiographic bone healing (P = 0.004) and higher bone volume (BV) [micro-computed tomography (micro-CT); P < 0.001]. The "same day" strategy represents a significant advance in the field of ex-vivo regional gene therapy because it offers a solution to limitations associated with the culture expansion process required in the traditional ex vivo approach. This strategy should be cost-effective when adapted for human use.
PMCID:3098640
PMID: 21343916
ISSN: 1525-0024
CID: 1667762

Superior labrum anterior to posterior tears and glenohumeral instability

Virk, Mandeep S; Arciero, Robert A
Cadaver experiments and clinical studies suggest that the superior labrum-biceps complex plays a role in glenohumeral stability. Superior labrum anterior to posterior (SLAP) tears can be present in acute and recurrent glenohumeral dislocations and contribute to glenohumeral instability. Isolated SLAP tears can cause instability, especially in throwing athletes. Diagnosing a SLAP tear on the basis of the clinical examination alone is difficult because of nonspecific history and physical examination findings and the presence of coexisting intra-articular lesions. Magnetic resonance arthrography is the imaging study of choice for diagnosing SLAP tears; however, arthroscopy remains the gold standard for diagnosis. Arthroscopy is the preferred technique for the repair of a type II SLAP tear and its variant types (V through X) in acute glenohumeral dislocations and instability in younger populations. Clinical outcome studies report a low recurrence of glenohumeral instability after the arthroscopic repair of a SLAP tear in addition to a Bankart repair. Long-term follow-up studies and further advances in arthroscopic fixation techniques will allow a better understanding and improvement in outcomes in patients with SLAP tears associated with glenohumeral instability.
PMID: 23395054
ISSN: 0065-6895
CID: 1667742

Systemic administration of sclerostin antibody enhances bone repair in a critical-sized femoral defect in a rat model

Virk, Mandeep S; Alaee, Farhang; Tang, Hezhen; Ominsky, Michael S; Ke, Hua Zhu; Lieberman, Jay R
BACKGROUND: Systemic administration of sclerostin neutralizing antibody has led to increased bone formation in animal models of osteoporosis. The purpose of this study was to determine if systemic administration of sclerostin neutralizing antibody could increase the healing response in a critical-sized femoral defect in rats. METHODS: Critical-sized femoral defects were created in Lewis rats, and the rats were randomized into four groups. The sclerostin antibody (Scl-Ab) treatment groups included the continuous Scl-Ab group (twenty-one animals), the early Scl-Ab group (fifteen animals), and the delayed Scl-Ab group (fifteen animals), which received sclerostin antibody (25 mg/kg) twice weekly for weeks 0 through 12; weeks 0 through 2; and weeks 2 through 4; respectively. Twenty-one animals in the control group received vehicle from weeks 0 through 12. In a subsequent study, bone turnover markers were measured at zero, two, six, and twelve weeks after surgery in rats receiving vehicle or sclerostin neutralizing antibody for twelve weeks (fifteen rats per group). The quality of bone formed was evaluated with radiographs, microcomputed tomography, biomechanical testing, and histologic and histomorphometric analysis. RESULTS: In the primary study, four of fifteen defects in the continuous (zero to twelve-week) Scl-Ab group, three of fifteen defects in the early (zero to two-week) Scl-Ab group, and four of fifteen defects in the delayed (two to four-week) Scl-Ab group healed at twelve weeks, while none of the defects healed in the control group. In both studies, treatment with sclerostin antibody for twelve weeks demonstrated a significant increase in new bone formation (p < 0.05) compared with the control group. The three treatment groups did not differ significantly with respect to the healing rates and the quality of new bone formed in the defect. The serum markers of bone formation were significantly elevated in the animals in the continuous Scl-Ab group (p < 0.05) compared with the controls. CONCLUSIONS: Administration of sclerostin neutralizing antibody led to increased bone formation, resulting in complete healing of femoral defects in a small subset of rats, with a majority of the animals not healing the defect by twelve weeks.
PMCID:3748979
PMID: 23595067
ISSN: 1535-1386
CID: 1667732

The future of healthcare service in orthopedic practice: Telemedicine or in-person visits?

Ben-Ari, Erel; Kirshenbaum, Joshua; Patel, Ruby G; Kwon, Young W; Rokito, Andrew S; Zuckerman, Joseph D; Virk, Mandeep S
BACKGROUND:The objective of this study is to assess patient satisfaction and preference for telemedicine- versus in-person visits for outpatient shoulder and elbow musculoskeletal consultation during the COVID-19 pandemic and in the future. METHODS:Patients who had telemedicine visits for shoulder and elbow musculoskeletal complaints at a single institution from March through June, 2020, were invited to respond to a post-visit survey. The survey included a standardized questionnaire that focused on the patient's satisfaction with the telemedicine visit(s) during the pandemic and preference for using the telemedicine platform in the future following the pandemic. Additional details regarding their virtual visits (severity of their medical condition, previous virtual- or ER visits) were also obtained. Data regarding patient demographics and visit details (primary diagnosis, type of visit, length of visit, treating physician) were extracted from electronic medical records. RESULTS:In total, 153 patients participated in the study. Overall, high satisfaction scores regarding the telemedicine visit were noted: 91% of patients reported that their concerns were adequately addressed, 89% would recommend telemedicine to a friend and 94% stated that they would use this platform again in the presence of a situation like the COVID-19 pandemic. However, the majority of patients (76%) reported a preference for in-person visits for the same musculoskeletal complaint if it were not for COVID-19. A telemedicine visit duration of more than 10 minutes and a first-time telemedicine visit correlated with higher satisfaction rates (P=0.037 and P=0.001, respectively). CONCLUSIONS:COVID-19 has provided a boost to the use of our telemedicine platform, with a high satisfaction rate among patients with shoulder and elbow musculoskeletal complaints, largely due to safety reasons and limited access to in-person doctor visits. However, a considerable number of patients would have preferred in-person visits for similar health complaints if there were no pandemic. Further research on optimizing the selection of patients for telemedicine visits and addressing their expectations and concerns regarding their visits will improve patients' preference for future telemedicine visits.
PMID: 34089879
ISSN: 1532-6500
CID: 4899382

Anesthesia in Total Shoulder Arthroplasty: A Systematic Review and Meta-Analysis

Boin, Michael A; Mehta, Devan; Dankert, John; Umeh, Uchenna O; Zuckerman, Joseph D; Virk, Mandeep S
»:For shoulder arthroplasty, regional anesthesia is safer when compared with general anesthesia. There is insufficient evidence to demonstrate the superiority of regional anesthesia with respect to pulmonary complications and hospital length of stay. »:Infiltration of the shoulder with local anesthetics offers no additional benefits compared with single-shot or continuous brachial plexus blocks for shoulder arthroplasty. »:There is high-quality evidence (Level I) demonstrating lower pain scores and lower perioperative opioid requirements after a continuous peripheral nerve block compared with a single-shot nerve block. However, catheter dislodgment and logistical issues with catheter insertion are impediments to the widespread usage of a continuous nerve block with an indwelling catheter. »:Liposomal bupivacaine is comparable with non-liposomal local anesthetic agents with respect to pain relief, the opioid-sparing effect, and adverse effects in the first 48 hours after total shoulder arthroplasty. »:Perioperative dexamethasone administration improves postoperative pain control, decreases perioperative opioid requirements, and reduces postoperative nausea.
PMID: 34757963
ISSN: 2329-9185
CID: 5050572

Radiographic and clinical characterization of coracoid fractures: a retrospective cohort analysis

Ben-Ari, Erel; Pines, Yaniv; Gordon, Dan; Zuckerman, Joseph D; Petchprapa, Catherine; Virk, Mandeep S
PURPOSE/OBJECTIVE:Coracoid fracture is a rare injury. The aim of this study is to present the demographics, clinical and radiologic characteristics, and outcomes of coracoid fracture in a cohort of 32 patients. METHODS:We queried our institutional electronic medical record database (years 2012-2020) to identify patients with coracoid fractures using specific International Classification of Disease-10 codes. Demographic data, injury details including mechanism of injury and associated injuries, imaging performed, and treatment outcomes were obtained from retrospective chart review. A radiologist reviewed all available imaging studies (radiographs/CT/MRI) and classified the fractures according to Ogawa and Eyres classifications. Missed diagnoses were determined by comparing initial imaging reports with the follow-up imaging obtained in the office. RESULTS:Thirty-two patients with coracoid fractures were identified during the study period. Sixteen fractures (50%) occurred in the setting of low-energy trauma. Twelve fractures were missed on initial radiographs, and diagnosis with three-view radiographs (AP, scapular-Y and axillary) was 88% compared to 33% (p < 0.03) with two views (AP, scapular-Y). The majority of fractures were non-displaced (94%), and 56% were Ogawa Type-II fractures. Associated injuries were seen in 81% of patients. Most fractures (94%) were treated without surgery with excellent outcomes. CONCLUSION/CONCLUSIONS:Coracoid fractures continue to be a rare injury. In contrast to previous studies, in this case series of 32 patients, half of the fractures were associated with low-energy trauma, which correlated with higher percentage of non-displaced fractures and Ogawa Type-II fractures. Addition of the axillary view in the trauma radiographic series significantly improved the initial fracture detection rate. LEVEL IV/UNASSIGNED:Retrospective study.
PMID: 34628533
ISSN: 1633-8065
CID: 5027112

Patient and Physician Satisfaction with Telehealth During the COVID-19 Pandemic: Sports Medicine Perspective

Kirby, David J; Fried, Jordan W; Buchalter, Daniel B; Moses, Michael J; Hurly, Eoghan T; Cardone, Dennis A; Yang, S Steven; Virk, Mandeep S; Rokito, Andrew S; Jazrawi, Laith M; Campbell, Kirk A
PMID: 33512302
ISSN: 1556-3669
CID: 4767672

Minimal clinically important difference, substantial clinical benefit, and patient acceptable symptom state of PROMIS upper extremity after total shoulder arthroplasty

Gordon, Dan; Pines, Yaniv; Ben-Ari, Erel; As, Rokito; Kwon, Young W; Zuckerman, Joseph D; Virk, Mandeep S
Background/UNASSIGNED:The Patient-Reported Outcomes Measurement Information System minimal clinically important difference (PROMIS MCID), substantial clinical benefit (SCB), and patient acceptable symptom state (PASS) of patient-reported outcome measures provide clinical significance to patient-reported outcome measures scores. The goal of this study is to measure the MCID, SCB, and PASS of PROMIS Upper Extremity v2.0 (PROMIS UE) in patients undergoing total shoulder arthroplasty (TSA). Methods/UNASSIGNED:All patients who underwent TSA since October 2017 were identified from our institutional database. Patients who had completed the PROMIS UE outcome measure before surgery were asked to complete a PROMIS UE and anchor survey that contained two transition questions to assess patient satisfaction and change in symptoms since treatment. The anchor-based MCID, SCB, and PASS were calculated as the change in PROMIS UE score that represented the optimal cutoff for a receiver operating characteristic curve. The distribution-based MCID was calculated as a range between the average standard error of measurement multiplied by 2 different constants: 1 and 2.77. Results/UNASSIGNED:This study enrolled 165 patients. The anchor-based MCID for PROMIS UE was calculated to be 8.05 with an AUC of 0.814. The anchor-based SCB was calculated to be 10.0 with an AUC of 0.727. The distribution-based MCID was calculated to be between 3.12 and 8.65. The PASS was calculated to be 37.2 with an AUC of 0.90. Conclusions/UNASSIGNED:The establishment of MCID, SCB, and PASS for PROMIS UE scores after shoulder arthroplasty provides meaningful and objective clinical interpretation of the improvements in outcome scores after TSA.
PMCID:8411069
PMID: 34505102
ISSN: 2666-6383
CID: 5006552

Complex Region Pain Syndrome Following Shoulder Surgery

Magone, Kevin M; Ben-Ari, Erel; Hacquebord, Jacques H; Virk, Mandeep S
Purpose/UNASSIGNED:To describe the clinical features, treatment, and outcomes in patients with complex region pain syndrome (CRPS) following shoulder surgeries. Methods/UNASSIGNED:Three patients were diagnosed with CRPS according to the Budapest criteria. Patients were followed up prospectively at regular intervals for a minimum of 2 years. Demographic data, clinical symptoms, physical examination findings, treatment received, and outcomes were collected and reported. Results/UNASSIGNED:The minimum time interval between surgery and diagnosis was 3 weeks (average, 8 weeks). The index procedures included 2 arthroscopic rotator cuff repairs and 1 open Latarjet. Neurologic pain, muscle spasms, hand and wrist swelling, and joint stiffness were seen in the shoulder, wrist, and hand, but the elbow was spared in all patients. Despite the use of multimodal treatment modalities, the symptoms were refractory to treatment for prolonged periods (range, 6-12 months). Hand and wrist symptoms took an average of 4 months longer than shoulder symptoms to improve. At the latest follow-up (range, 24-26 months), varying degrees of residual hand dysfunction, pain, and inability to make a fist or fully extend the fingers were noted in all 3 patients. Conclusions/UNASSIGNED:CPRS type 1 following shoulder surgery is a disabling condition with a long-protracted clinical course. CRPS can present as early as few weeks after shoulder surgery, with symptoms of neuropathic pain, spasm, and stiffness affecting the entire upper-extremity joints except the elbow. CRPS symptoms resolve earlier in the shoulder compared with the wrist and hand, with pain improving first, followed by recovery of motion and function. Residual stiffness affecting grip function is last to recover and can present up to 2 years after onset of symptoms. Although prompt recognition and multimodal approach are considered the mainstay of treatment, there is no gold standard treatment modality that can reproducibly alter the natural history of CRPS. Level of Evidence/UNASSIGNED:IV, therapeutic case series.
PMCID:8365219
PMID: 34430883
ISSN: 2666-061x
CID: 4989082

No difference in 90-day complication rate following open versus arthroscopic Latarjet procedure

Hurley, Eoghan T; Manjunath, Amit K; Matache, Bogdan A; Jia, Nathan W; Virk, Mandeep; Jazrawi, Laith M; Meislin, Robert J
The purpose of this study was to compare the 90-day complication rate between the open and arthroscopic Latarjet procedure. A retrospective review of patients who underwent an open or arthroscopic Latarjet procedure at NYU Langone Health between 2012 and 2019 was performed. The complications, readmissions, and reoperations within 90 days were assessed. Outcomes were compared between the two approaches, and a p value of < 0.05 was considered to be statistically significant. The study included 150 patients (open: 110; arthroscopic: 40), with no patients lost to follow-up within the first 90 days. Both cohorts were similar in terms of patient demographics. No intra-operative complications were observed in either group. Overall, there were 4 post-operative complications with the open approach and 2 with the arthroscopic approach (3.6% and 5.0%, respectively; n.s.) during the study period. Three patients required a readmission within the 90-day period; one patient in both groups required a revision Latarjet for graft fracture, and one patient in the open Latarjet required irrigation and debridement for deep infection (n.s.). With the open approach, there were 2 (2.3%) wound complications, 1 graft complication, and 1 (1.1%) nerve injury. With the arthroscopic approach, there was 1 (2.8%) wound complication and 1 (2.8%) hardware complication. The safety, and 90-day complication and readmission profile of arthroscopic Latarjet is similar to open Latarjet procedure. LEVEL OF EVIDENCE: Level III.
PMID: 33025054
ISSN: 1433-7347
CID: 4626882